Chinese Medicine Neuroaid Efficacy on Stroke Recovery

Abstract

Background and Purpose— Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window. Methods— This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health Stroke Scale, presence of cortical signs, and antiplatelet use. Results— The modified Rankin Scale shift analysis–adjusted odds ratio was 1.09 (95% confidence interval, 0.86–1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups. Conclusions— MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00554723.

Effects of MLC601 on Early Vascular Events in Patients After Stroke

“…9 Poststroke use of secondary prevention treatments and rehabilitation were similar between the 2 groups ( Table 1). The numbers of atrisk subjects, that is, those who had not experienced events and were not lost to follow-up, at each time point are shown in the Figure. Overall, the composite vascular outcome occurred in 47 (4.3%) subjects during the 3-month follow-up period: 16 (2.9%) subjects in the MLC601 group and 31 (5.6%) subjects in the placebo group (odds ratio, 0.50; 95% CI, 0.27-0.93; RD, −2.7%; 95% CI, −5.1% to −0.4%]; Table 2).…”

“…9 Although early vascular events were associated with poorer mRS, and a reduction in such vascular events with treatment should improve functional outcome, this was not detected statistically in the primary analysis of the CHIMES study, presumably because of dilution by other factors. 9 Only a limited number of treatments have been shown to reduce early recurrent vascular events after acute stroke. Aspirin produced a small but important reduction of ≈10 deaths or recurrent strokes per 1000.…”

“…Previous studies of MLC601 in normal subjects and patients with stroke showed neither antiplatelet effects nor interaction with aspirin. Moreover, because no difference in hemorrhagic events between MLC601 and placebo was detected in the CHIMES study, 9 it seems unlikely that an antithrombotic effect of MLC601 can be an explanatory mechanism, nor does MLC601 have any known effect on blood pressure or lipids. It is possible that the effect of MLC601 on ATP-dependent potassium channel activation may provide myocardial and cerebral preconditioning and hence chronic cytoprotection.…”

“…9 Subjects were allocated to either MLC601 or placebo for 3 months, in addition to standard stroke care, for example, antiplatelet therapy, control of vascular risk factors, and appropriate rehabilitation. Subjects were assessed on 3 follow-up visits when occurrence of any adverse events was recorded.…”

Comparison Between the Original and Shortened Versions of the National Institutes of Health Stroke Scale in Ischemic Stroke Patients of Intermediate Severity

“…10,11 Patients were randomly allocated to either MLC601 or placebo for 3 months as add-on to standard stroke care.Patients were assessed at baseline, day 10 (±2 days), or discharge, whichever was earlier, and month 3 (±1 week). At baseline, demographic and clinical information, as well as prestroke modified Rankin Scale (mRS) score, were ascertained.…”